Argininamide binding arrests global motions in HIV-1 TAR RNA: Comparison with Mg2+-induced conformational stabilization Journal Article
| Authors: | Pitt, S. W.; Majumdar, A.; Serganov, A.; Patel, D. J.; Al-Hashimi, H. M. |
| Article Title: | Argininamide binding arrests global motions in HIV-1 TAR RNA: Comparison with Mg2+-induced conformational stabilization |
| Abstract: | The structure and dynamics of the stem-loop transactivation response element (TAR) RNA from the human immunodeficiency virus type-1 (HIV-1) bound to the ligand argininamide (ARG) has been characterized using a combination of a large number of residual dipolar couplings (RDCs) and trans-hydrogen bond NMR methodology. Binding of ARG to TAR changes the average inter-helical angle between the two stems from ∼47° in the free state to ∼11° in the bound state, and leads to the arrest of large amplitude (±46°) inter-helical motions observed previously in the free state. While the global structural dynamics of TAR-ARG is similar to that previously reported for TAR bound to Mg2+, there are substantial differences in the hydrogen bond alignment of bulge and neighboring residues. Based on a novel H5(C5)NN experiment for probing hydrogen-mediated 2hJ(N,N) scalar couplings as well as measured RDCs, the TAR-ARG complex is stabilized by a U38-A27·U23 base-triple involving an A27·U23 reverse Hoogsteen hydrogen bond alignment as well as by a A22-U40 Watson-Crick base-pair at the junction of stem I. These hydrogen bond alignments are not observed in either the free or Mg2+ bound forms of TAR. The combined conformational analysis of TAR under three states reveals that ligands and divalent ions can stabilize similar RNA global conformations through distinct interactions involving different hydrogen bond alignments in the RNA. © 2004 Elsevier Ltd. All rights reserved. |
| Keywords: | unclassified drug; nonhuman; protein binding; rna; magnetic resonance spectroscopy; hydrogen bond; hydrogen bonding; models, molecular; solutions; binding sites; human immunodeficiency virus; nucleic acid conformation; recognition; dna responsive element; ligand binding; arginine; rna, viral; trans isomer; human immunodeficiency virus 1; hiv-1; magnesium; nmr; residual dipolar couplings; adaptation; rna conformation; hiv long terminal repeat; arginine derivative; humans; priority journal; article; arg, argininamide; collective motions; hiv, human immunodeficiency virus; rdc, residual dipolar coupling; rmsd, root-mean-square deviation; tar, transactivation response element; argininamide |
| Journal Title: | Journal of Molecular Biology |
| Volume: | 338 |
| Issue: | 1 |
| ISSN: | 0022-2836 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 2004-04-16 |
| Start Page: | 7 |
| End Page: | 16 |
| Language: | English |
| DOI: | 10.1016/j.jmb.2004.02.031 |
| PROVIDER: | scopus |
| PUBMED: | 15050819 |
| PMCID: | PMC4694592 |
| DOI/URL: | |
| Notes: | J. Mol. Biol. -- Cited By (since 1996):51 -- Export Date: 16 June 2014 -- CODEN: JMOBA -- Source: Scopus |
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